Immune-checkpoint inhibitors (ICIs) are a standard treatment in advanced non-small cell lung cancer (NSCLC). However, ICIs can induce immune-related adverse events (irAEs) that may compromise treatment continuation. Here we report our experience in patients with NSCLC, the incidence of irAEs and its correlation with efficacy.

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Method

We have retrospectively analyzed 101 patients with advanced NSCLC receiving ICIs in our institution from March 2014 to January 2018. IrAEs were graded following CTCAE v4.0. Kaplan Meier and log-rank tests were used to evaluate progression-free (PFS) and overall survival (OS). Analyses were performed using SPSS v24 package.

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Result

Median age was 66.4 [37-85] years, 74.3% were male. 33 (32.7%) patients presented squamous and 68 (67.3%) non-squamous histology. Most frequent ICIs were nivolumab (50%), pembrolizumab (31%) and atezolizumab (16%), used as monotherapy (79.2%) or in combination with chemotherapy (20.8%). 37.6% patients were treated with ICIs in first line setting, while 62.4% in second or beyond. Median duration of treatment was 2.7 [0.6-26.2] months.

Patients receiving ICIs in second line or beyond experienced significantly less irAEs (54.1%) than those treated in first line (73.7%), p 0.04.

47 (46.5%) patients received systemic corticosteroids during immunotherapy, 29.8% for irAEs management. 11 patients (10.9%) discontinued treatment due to irAEs. At the time of data analysis, 86.8% of irAEs had improved.

With a median follow-up of 8.9 [0.6-48.2] months, median OS was superior in patients experiencing irAEs: not reached (NR) vs 7.8 [95%CI, 5.2-10.5] months (p 0.001). Similarly, PFS was significantly longer: 6.2 [95%CI, 2.3-10.1] vs 2.7 [95%CI, 1.8-3.5] months (p <0.0001). OS was higher in patients who did not receive steroids during ICIs therapy: NR vs 9.9 [95%CI, 6.8-13.0] months (p 0.024). No association was found between efficacy and the use of antibiotics in the 3 months before first ICIs injection or during treatment.

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Conclusion

In our series, the presence of irAEs in patients with advanced NSCLC treated with ICIs was associated with efficacy in terms of PFS and OS. A negative correlation between usage of systemic corticosteroids and outcomes was found.